B Cell Overview

In autoimmune disease, the body no longer tolerates itself and its B cells regard certain tissues, cells, or proteins as if they were foreign invaders and attack them by producing antibodies. The consequences of this autoantibody production can be devastating. In lupus, antibodies to double-stranded DNA destroy the kidney. In antibody-mediated thrombosis antibodies to a key protein in the blood leads to stroke, heat attack, deep vein thrombosis and recurrent fetal loss.

B cells

Daily, the human body produces millions of uniquely different B cells, each with the potential to recognize and eliminate a different invading antigen, such as those found on a bacterium or virus. Each B cell produces antibodies against a specific molecular structure on the antigen's surface. Rather than targeting bacteria or viruses, occasionally B cells incorrectly identify certain body cells or proteins as foreign.

When functioning properly, the immune system distinguishes between its own tissues and foreign antigens. The two fundamental immune responses, antibody-mediated and cell-mediated, are controlled by two types of white blood cells, B cells and T cells, respectively. T cells rid the body of cells that have become infected or cancerous. B cells provide antibody-mediated immunity that eliminates circulating infectious agents and other foreign antigens.

B cells produce antibodies that recognize and bind to antigens and mark them for destruction. Each B cell type makes only one kind of antibody. An antibody binds to a specific structure on an antigen's surface called an epitope. The B cell also displays this antibody on its membrane as a receptor for the antigen.

Tolerizing B cells

B cells are normally triggered to produce antibodies by a two-step process. After a B cells encounters an antigen, these partially activated B cells migrate through the lymphoid tissue. If an activated B cell encounters a T cell that has been activated by the same antigen, antibodies against that antigen are produced. If the B cell does not receive the corresponding T cell signal, it will become inactive or die.

Immune tolerance is a natural mechanism that eliminates development of B cells that target "self," rather than foreign antigens. La Jolla Pharmaceutical Company employs the concept of B cell tolerance to make proprietary Toleragens®, molecules which are engineered to kill or inactivate development of pathogenic B cells. Toleragens are thought to deliver a specific and potent B cell signal, but not a T cell signal. Thus, binding of a Toleragen to a specific B cell is thought to stop production of pathogenic antibodies and causes the cell to die or become inactive. That is, the B cell has become "tolerized" to a particular antigen.

Toleragens are composed of multiple copies of B cell epitopes attached to a non-immunogenic carrier platform. The same basic, non-immunogenic carrier platform is designed to be used with different epitopes to make a variety of Toleragens to treat a variety of autoimmune diseases.

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